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Publication : Nox2 and p47(phox) modulate compensatory growth of primary collateral arteries.

First Author  DiStasi MR Year  2014
Journal  Am J Physiol Heart Circ Physiol Volume  306
Issue  10 Pages  H1435-43
PubMed ID  24633549 Mgi Jnum  J:211551
Mgi Id  MGI:5575671 Doi  10.1152/ajpheart.00828.2013
Citation  DiStasi MR, et al. (2014) Nox2 and p47(phox) modulate compensatory growth of primary collateral arteries. Am J Physiol Heart Circ Physiol 306(10):H1435-43
abstractText  The role of NADPH oxidase (Nox) in both the promotion and impairment of compensatory collateral growth remains controversial because the specific Nox and reactive oxygen species involved are unclear. The aim of this study was to identify the primary Nox and reactive oxygen species associated with early stage compensatory collateral growth in young, healthy animals. Ligation of the feed arteries that form primary collateral pathways in rat mesentery and mouse hindlimb was used to assess the role of Nox during collateral growth. Changes in mesenteric collateral artery Nox mRNA expression determined by real-time PCR at 1, 3, and 7 days relative to same-animal control arteries suggested a role for Nox subunits Nox2 and p47(phox). Administration of apocynin or Nox2ds-tat suppressed collateral growth in both rat and mouse models, suggesting the Nox2/p47(phox) interaction was involved. Functional significance of p47(phox) expression was assessed by evaluation of collateral growth in rats administered p47(phox) small interfering RNA and in p47(phox-/-) mice. Diameter measurements of collateral mesenteric and gracilis arteries at 7 and 14 days, respectively, indicated no significant collateral growth compared with control rats or C57BL/6 mice. Chronic polyethylene glycol-conjugated catalase administration significantly suppressed collateral development in rats and mice, implying a requirement for H2O2. Taken together, these results suggest that Nox2, modulated at least in part by p47(phox), mediates early stage compensatory collateral development via a process dependent upon peroxide generation. These results have important implications for the use of antioxidants and the development of therapies for peripheral arterial disease.
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